Urothelial CarcinomaEarly Phase 1NCT03208712
Radium-223 and Atezolizumab in Patients With Urothelial Carcinoma With Bone Metastases Who Have Had Disease Progression After Platinum-Based Chemotherapy
A Early Phase 1 study testing Atezolizumab and Radium-223 in people with Urothelial Carcinoma, run by University of Michigan Rogel Cancer Center at 1 site in United States.
Trial summary
This is a single-arm, single-site pilot of Radium-223 (55 kBq/kg) IV q3 weeks for up to 6 doses in combination with Atezolizumab 1200mg IV once every 3 weeks until investigator determined lack of benefit, unacceptable toxicity, or 17 doses in patients with urothelial carcinoma with bone metastases who have disease… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urothelial Carcinoma
- What is being tested?
- Atezolizumab and Radium-223
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2017to 2 Aug 2018
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must have a histologic diagnosis of urothelial carcinoma with radiologic, histologic or cytologic evidence of metastatic disease.
- Subjects must have at least 1 bone metastasis of any size on imaging.
- ECOG performance status of 0- 2 (Eastern Cooperative Oncology Group Performance Status: an attempt to quantify cancer patients' general well-being and activities of daily life. The score ranges from 0 to 5 where 0 is asymptomatic and 5 is death.)
- Subjects must have progression of disease within 12 months of platinum-containing chemotherapy (chemotherapy could have been given in the neoadjuvant, adjuvant or metastatic settings) for urothelial cancer.
- Adequate organ and marrow function Subjects must have measurable disease on physical exam or imaging per RECIST 1.1 criteria.
- Recovery to baseline or < Grade 1 CTCAE v.4.03 from toxicities related to any prior treatments, unless AE(s) are clinically non-significant and/or stable on supportive therapy
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- Patients must be ≥ 2 weeks from most recent systemic therapy or radiation therapy.
- Women of childbearing potential must have a negative serum pregnancy test within 28 days prior to registration.
- Female subjects of childbearing potential and their male partners, and male subjects must be willing to use a highly effective method of contraception from the time consent is signed until 6 months after treatment discontinuation.
- Ability to understand and the willingness to sign a written informed consent
- Age ≥ 18 years
- Life expectancy ≥ 12 weeks
- Able to comply with study protocol, in the investigator's judgment
Who cannot join
- Prior treatment with anti-PD-1/PD-L1, and anti-CTLA-4 is NOT allowed. Prior intravesical BCG therapy is allowed.
- Treatment with any investigational agent or on an interventional clinical trial within 30 days prior to treatment on protocol
- No prior or concurrent malignancy is allowed except for: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, localized or locally advanced prostate cancer definitively treated without recurrence or with biochemical recurrence only, or any other cancer fully treated or from which the subject has been disease-free for at least 2 years.
- Autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematosus. Note: Vitiligo, mild psoriasis (topical therapy only) or hypothyroidism are allowed.
- Need for systemic corticosteroids > 10 mg prednisone daily or equivalent alternative steroid (except physiologic dose for adrenal replacement therapy) or other immunosuppressive agents (such as cyclosporine or methotrexate). Use of topical and inhaled corticosteroids is permitted.
- Any history of allografts
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- General Medical Exclusions
- Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome)
- Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to enrollment, unstable arrhythmias, or unstable angina. Patients with known left ventricular ejection fraction (LVEF) <40% will be excluded.
- Severe infection within 4 weeks prior to initiation of study treatment, including but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
- Treatment with therapeutic oral or IV antibiotics within 14 days prior to initiation of study treatment. Patients receiving prophylactic antibiotics (e.g. for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
- Major surgical procedure within 4 weeks prior to initiation of study treatment of anticipation of need for a major surgical procedure during the course of the study other than for diagnosis
- History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
- History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
- Positive test for HIV
- Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C.
- Active tuberculosis
- Administration of a live, attenuated vaccine within 4 weeks prior to initiation of study treatment with atezolizumab or anticipation that such a live, attenuated vaccine will be required during the study.
- Bone marrow dysplasia
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
About this study
Official title: Pilot Trial of Radium-223 and Atezolizumab in Patients With Urothelial Carcinoma With Bone Metastases Who Have Had Disease Progression After Platinum-Based Chemotherapy
This is a single-arm, single-site pilot of Radium-223 (55 kBq/kg) IV q3 weeks for up to 6 doses in combination with Atezolizumab 1200mg IV once every 3 weeks until investigator determined lack of benefit, unacceptable toxicity, or 17 doses in patients with urothelial carcinoma with bone metastases who have disease progression after platinum-containing chemotherapy.
- Conditions
- Urothelial Carcinoma
- Being tested
- Atezolizumab, Radium-223
- Medical subject headings
- Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtezolizumabDrug
Atezolizumab 1200 mg IV once every 3 weeks
Radium-223Drug
Radium- 223 IV (55 kBq/kg) every 3 weeks for up to 6 doses
| Study group | Role | What they receive |
|---|---|---|
| Radium-223 and Atezolizumab | Experimental | Radium- 223 IV (55 kBq/kg) every 3 weeks for up to 6 doses
Atezolizumab 1200 mg IV once every 3 weeks until investigator determined lack of benefit, unacceptable toxicity, or 17 doses Receives: Drug: Atezolizumab; Drug: Radium-223 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent of Patients that respond to Treatment
Primary efficacy will be measured by Objective Response Rate (Complete Response + Partial Response). Complete response will be defined as the disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions. Partial Response will be defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions.
Measured: Up to 52 weeks
Secondary outcomes (4)
Median Overall Survival Time
Measured: Up to 52 weeks
Median Progression Free Survival Time
Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression.
Measured: Up to 52 weeks
Number of Patients with Complete Response
Complete Response (CR): Disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions.
Measured: Up to 52 weeks
Change in QOL Score From Baseline
Quality of life as assessed by the EORTC QLQ-C30 (A questionnaire developed by the European Organization for Research and Treatment of Cancer to assess the quality of life of cancer patients) at baseline and during treatment will be described using means or medians and associated measures of variability.
Measured: Up to 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2017
- Study start1 Nov 2017
- Primary completion2 Aug 2018
- Study completion2 Aug 2018
Why it stopped: Low accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Pilot Study
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ajjai Alva, M.D., Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03208712
- Sponsor's protocol ID
- UMCC 2017.023
- Other IDs
- HUM00126822
- Status last verified
- Oct 2018
- First submitted
- 3 Jul 2017
- Last updated
- 24 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Trial of Radium-223 and Atezolizumab in Patients With Urothelial Carcinoma With Bone Metastases Who Have Had Disease Progression After Platinum-Based Chemotherapy
- ClinicalTrials.gov ID
- NCT03208712
- Acronym / sponsor ID
- UMCC 2017.023
- Conditions
- Urothelial Carcinoma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low accrual
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Study start
- 1 Nov 2017 (actual)
- Primary completion
- 2 Aug 2018 (actual)
- Study completion
- 2 Aug 2018 (actual)
- First posted
- 5 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-arm, single-site pilot of Radium-223 (55 kBq/kg) IV q3 weeks for up to 6 doses in combination with Atezolizumab 1200mg IV once every 3 weeks until investigator determined lack of benefit, unacceptable toxicity, or 17 doses in patients with urothelial carcinoma with bone metastases who have disease progression after platinum-containing chemotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Pilot Study
| Arm | Type | Receives |
|---|---|---|
| Radium-223 and Atezolizumab | Experimental | Drug: Atezolizumab, Drug: Radium-223Radium- 223 IV (55 kBq/kg) every 3 weeks for up to 6 doses Atezolizumab 1200 mg IV once every 3 weeks until investigator determined lack of benefit, unacceptable toxicity, or 17 doses |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Subjects must have a histologic diagnosis of urothelial carcinoma with radiologic, histologic or cytologic evidence of metastatic disease.
- Subjects must have at least 1 bone metastasis of any size on imaging.
- ECOG performance status of 0- 2 (Eastern Cooperative Oncology Group Performance Status: an attempt to quantify cancer patients' general well-being and activities of daily life. The score ranges from 0 to 5 where 0 is asymptomatic and 5 is death.)
- Subjects must have progression of disease within 12 months of platinum-containing chemotherapy (chemotherapy could have been given in the neoadjuvant, adjuvant or metastatic settings) for urothelial cancer.
- Adequate organ and marrow function Subjects must have measurable disease on physical exam or imaging per RECIST 1.1 criteria.
Key exclusion criteria (20 listed)
- Prior treatment with anti-PD-1/PD-L1, and anti-CTLA-4 is NOT allowed. Prior intravesical BCG therapy is allowed.
- Treatment with any investigational agent or on an interventional clinical trial within 30 days prior to treatment on protocol
- No prior or concurrent malignancy is allowed except for: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, localized or locally advanced prostate cancer definitively treated without recurrence or with biochemical recurrence only, or any other cancer fully treated or from which the subject has been disease-free for at least 2 years.
- Autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematosus. Note: Vitiligo, mild psoriasis (topical therapy only) or hypothyroidism are allowed.
- Need for systemic corticosteroids > 10 mg prednisone daily or equivalent alternative steroid (except physiologic dose for adrenal replacement therapy) or other immunosuppressive agents (such as cyclosporine or methotrexate). Use of topical and inhaled corticosteroids is permitted.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AtezolizumabAtezolizumab 1200 mg IV once every 3 weeks | Drug | Radium-223 and Atezolizumab |
| Radium-223Radium- 223 IV (55 kBq/kg) every 3 weeks for up to 6 doses | Drug | Radium-223 and Atezolizumab |
Primary outcome
Percent of Patients that respond to Treatment
Time frame: Up to 52 weeks
Primary efficacy will be measured by Objective Response Rate (Complete Response + Partial Response). Complete response will be defined as the disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions. Partial Response will be defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions.
4 secondary outcomes
Median Overall Survival Time
Time frame: Up to 52 weeks
Median Progression Free Survival Time
Time frame: Up to 52 weeks
Number of Patients with Complete Response
Time frame: Up to 52 weeks
Change in QOL Score From Baseline
Time frame: Up to 52 weeks
Results and safety
The study was stopped early (reason given: Low accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2018.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ajjai Alva, M.D. principal investigator
University of Michigan Rogel Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Atezolizumab and Radium-223 in people with Urothelial Carcinoma, run by University of Michigan Rogel Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Low accrual). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent of Patients that respond to Treatment (time frame: Up to 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2018.